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Cited by 14Erythropoietin and Anemia TreatmentHeat shock proteins researchHematopoietic Stem Cell Transplantation

Mortalin is a novel mediator of erythropoietin signaling

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Ohtsuka, Rie, Abe, Yasunobu, Fujii, Tomomi, Yamamoto, Masahiro, Nishimura, Junji, Takayanagi, Ryoichi, Muta, Koichiro·2007·European Journal of Haematology
DOI 10.1111/j.1600-0609.2007.00870.x
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Abstract

Erythropoietin (EPO) stimulates erythroid growth by enhancing the proliferation, maturation and survival of late‐stage erythroid progenitor cells. However, the entire process of EPO stimulation remains undetermined. To further clarify the intracellular mechanisms by which EPO affects the growth of erythroid progenitor cells, we analyzed proteins obtained from purified human erythroid colony‐forming cells (ECFCs) cultured with or without EPO, and one of the proteins apparently related with EPO stimuli was identified as mortalin (mthsp70/PBP74/Grp75/mot‐2), which is a member of the heat shock protein 70 family of chaperones. The amount of mortalin mRNA in ECFCs increased in an EPO dose‐dependent manner, and ECFC growth was dependent on the amount of mortalin. Furthermore, expression of mortalin in ECFCs was suppressed by a phosphatidylinositol 3‐kinase inhibitor. Finally, we analyzed gene expression patterns in ECFCs cultured with or without EPO after treatment with mortalin small interfering RNA (siRNA) using a DNA microarray. When ECFCs treated with mortalin siRNA were cultured with EPO, the expression of several genes overlapped with the profile seen in control ECFCs cultured without EPO. Our data suggest that mortalin is involved in the mediation of EPO signaling and plays an important role in stimulating the growth of erythroid progenitor cells.

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  • The hsp70 protein family and the HSPA9 gene play a role as a downstream mediator of erythropoietin signaling and contribute to normal erythropoiesis.

    “Moreover, the hsp70 protein family and the heat shock 70kDa protein 9 (HSPA9) gene play a role as a downstream mediator of erythropoietin signaling and contribute to normal erythropoiesis (Singh et al., 1997; Ran et al., 2000; Ohtsuka et al., 2007; Chen et al., 2011).”

    From Identification of Candidate Signature Genes and Key Regulators Associated With Trypanotolerance in the Sheko Breed (2019) · cites this paper as Ohtsuka et al., 2007

    The Discussion (page unavailable) identifies mortalin, an hsp70-family protein, as mediating EPO signaling and shows that changing its expression affects growth of cultured human erythroid progenitor cells. The paper does not establish that the hsp70 family as a whole has this role, explicitly identify HSPA9, or demonstrate a contribution to normal erythropoiesis in vivo. (LLM, conf=0.86)

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Authors
Ohtsuka, R., Abe, Y., Fujii, T., Yamamoto, M., Nishimura, J., Takayanagi, R., & Muta, K.
Affiliations
  • Kyushu University (JP)
  • National Kyushu Medical Center (JP)
  • Medical Institute of Bioregulation, Kyushu University (JP)
Corresponding author
Muta, Koichiro
ORCID
Venue
European Journal of Haematology
Publisher
Wiley
Published
2007-06-19
Volume
79
Issue
2
Pages
114-125
ISSN
  • 0902-4441 (ISSN-L)
  • 1600-0609
DOI
10.1111/j.1600-0609.2007.00870.x
OpenAlex
W2077497190
Cited by
14
References
0
Citations by year
2020: 1 · 2019: 1 · 2016: 1 · 2014: 1 · 2013: 1 · 2012: 2
FWCI
1.28
Type
journal article
Language
en
Open access
Licence
onlinelibrary.wiley.com/termsAndConditions#vor (vor)
Locations
  • European Journal Of Haematology (publishedVersion)
  • PubMed (publishedVersion)
Funders
Japan Society for the Promotion of Science
Topics
  • Health Sciences › Medicine › Hematology › Erythropoietin and Anemia Treatment
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Heat shock proteins research
  • Health Sciences › Medicine › Hematology › Hematopoietic Stem Cell Transplantation
Keywords
mortalin, erythropoietin signaling, erythroid colony-forming cells, erythroid progenitor cells, HSP70, phosphatidylinositol 3-kinase, gene expression profiling, erythropoiesis, siRNA knockdown
MeSH terms
Erythropoietin, Gene Expression Regulation, Humans, RNA, Messenger, Electrophoresis, Gel, Two-Dimensional, Down-Regulation, Erythroid Precursor Cells, Up-Regulation, HSP70 Heat-Shock Proteins, Phosphatidylinositol 3-Kinases, Oligonucleotide Array Sequence Analysis, MAP Kinase Signaling System, RNA, Small Interfering, Proto-Oncogene Proteins c-akt

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